20-17494045-T-G

Variant names:

• chr20-17494045-T-G
• rs6105762
• NM_001195.5:c.*29A>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001195.5(BFSP1):​c.*29A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.519 in 1,560,820 control chromosomes in the GnomAD database, including 211,766 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.50 (19166 hom., cov: 33)
  • Exomes 𝑓: 0.52 (192600 hom.)
• Consequence: BFSP1 NM_001195.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0530
• Publications: 12 publications found

Genes affected

BFSP1 (HGNC:1040): (beaded filament structural protein 1) This gene encodes a lens-specific intermediate filament-like protein named filensin. The encoded protein is expressed in lens fiber cells after differentiation has begun. This protein functions as a component of the beaded filament which is a cytoskeletal structure found in lens fiber cells. Mutations in this gene are the cause of autosomal recessive cortical juvenile-onset cataract. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]

BFSP1 Gene-Disease associations (from GenCC):

• cataract 33

  Inheritance: AR, AD, SD Classification: STRONG, MODERATE, LIMITED Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
• early-onset nuclear cataract

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 20-17494045-T-G is Benign according to our data. Variant chr20-17494045-T-G is described in ClinVar as [Benign]. Clinvar id is 1283614.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.552 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BFSP1	NM_001195.5	c.*29A>C		3_prime_UTR_variant	Exon 8 of 8	ENST00000377873.8	NP_001186.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BFSP1	ENST00000377873.8	c.*29A>C		3_prime_UTR_variant	Exon 8 of 8	1	NM_001195.5	ENSP00000367104.3
BFSP1	ENST00000377868.6	c.*29A>C		3_prime_UTR_variant	Exon 8 of 8	1		ENSP00000367099.2
BFSP1	ENST00000536626.7	c.*29A>C		3_prime_UTR_variant	Exon 9 of 9	2		ENSP00000442522.1

Frequencies

GnomAD3 genomes AF: 0.501 AC: 76167 AN: 151952 Hom.: 19135 Cov.: 33

Gnomad AFR AF: 0.450

Gnomad AMI AF: 0.479

Gnomad AMR AF: 0.524

Gnomad ASJ AF: 0.541

Gnomad EAS AF: 0.464

Gnomad SAS AF: 0.570

Gnomad FIN AF: 0.468

Gnomad MID AF: 0.532

Gnomad NFE AF: 0.528

Gnomad OTH AF: 0.515

GnomAD2 exomes AF: 0.522 AC: 117578 AN: 225236 AF XY: 0.522

Gnomad AFR exome AF: 0.443

Gnomad AMR exome AF: 0.586

Gnomad ASJ exome AF: 0.560

Gnomad EAS exome AF: 0.468

Gnomad FIN exome AF: 0.464

Gnomad NFE exome AF: 0.524

Gnomad OTH exome AF: 0.514

GnomAD4 exome AF: 0.521 AC: 734369 AN: 1408750 Hom.: 192600 Cov.: 26 AF XY: 0.522 AC XY: 364947 AN XY: 698578

African (AFR) AF: 0.448 AC: 14109 AN: 31516

American (AMR) AF: 0.570 AC: 22442 AN: 39378

Ashkenazi Jewish (ASJ) AF: 0.556 AC: 13172 AN: 23694

East Asian (EAS) AF: 0.441 AC: 17310 AN: 39286

South Asian (SAS) AF: 0.559 AC: 44590 AN: 79766

European-Finnish (FIN) AF: 0.466 AC: 24303 AN: 52108

Middle Eastern (MID) AF: 0.491 AC: 2708 AN: 5512

European-Non Finnish (NFE) AF: 0.524 AC: 565716 AN: 1079320

Other (OTH) AF: 0.516 AC: 30019 AN: 58170

GnomAD4 genome AF: 0.501 AC: 76243 AN: 152070 Hom.: 19166 Cov.: 33 AF XY: 0.502 AC XY: 37342 AN XY: 74344

African (AFR) AF: 0.451 AC: 18690 AN: 41466

American (AMR) AF: 0.525 AC: 8024 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.541 AC: 1879 AN: 3472

East Asian (EAS) AF: 0.464 AC: 2397 AN: 5170

South Asian (SAS) AF: 0.570 AC: 2742 AN: 4812

European-Finnish (FIN) AF: 0.468 AC: 4953 AN: 10588

Middle Eastern (MID) AF: 0.537 AC: 158 AN: 294

European-Non Finnish (NFE) AF: 0.528 AC: 35884 AN: 67956

Other (OTH) AF: 0.512 AC: 1080 AN: 2108

Alfa AF: 0.524 Hom.: 27196

Bravo AF: 0.502

Asia WGS AF: 0.518 AC: 1805 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Jun 29, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.0
DANN	Benign	0.53
PhyloP100		0.053
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs6105762; hg19: chr20-17474690; COSMIC: COSV64900539;